This invention relates to the purification of epoxidation reaction mixtures. In particular, the invention pertains to the recovery of a chiral epoxy alcohol or chiral epoxy alcohol derivative having high optical purity. The transition metal catalyzed epoxidation of ethylenically unsaturated substrates using organic hydroperoxides as oxidants is a well known method for the preparation of epoxides. In one variation of this technology, optically active epoxy alcohols are prepared by reacting unsaturated alcohols with organic hydroperoxides in the presence of transition metal catalysts containing chiral ligands. The optically active epoxy alcohol products are of great value as intermediates in the synthesis of compounds having high physiological activity.
However, the recovery of pure epoxy alcohols from crude epoxidation reaction mixtures is complicated by the numerous components typically present in such mixtures. The reaction mixture will normally contain a major amount of a first chiral epoxy alcohol, a minor amount of a second chiral epoxy alcohol which is an enantiomer of the first chiral epoxy alcohol, unreacted organic hydroperoxide, unreacted unsaturated alcohol, transition metal catalyst, the organic alcohol coproduct derived from the reacted hydroperoxide, and solvent. Epoxy alcohols tend to be highly reactive and susceptible to decomposition at elevated temperatures, particularly in the presence of Lewis acids such as the transition metal compounds typically used as catalysts in epoxidation reactions.
Moreover, the methods developed to date for the asymmetric epoxidation of unsaturated substrates are not completely stereoselective. That is, both possible stereoisomers of the epoxy alcohol are generated, yielding a reaction product having an enantiomeric excess less than the maximum theoretically possible. Since the physiological activities of the epoxy alcohol product and its derivatives are generally directly related to optical purity, it is highly desirable to obtain a chiral epoxy alcohol having an enantiomeric excess as close as possible to 100%. Conventional physical methods of separation such as fractional distillation, fractional crystallization, extraction, and the like are normally not particularly effective in separating enantiomers either because the optical isomers have very similar physical properties (e.g., solubility, boiling point, melting point) or because of uneconomical losses during purification. Clearly, there is a need for a practical method whereby a chiral epoxy alcohol having enhanced optical purity may be efficiently recovered from an epoxidation reaction mixture.